Barbiturate-derived antiepileptic Pregnancy: Primidone is extensively metabolised to phenobarbital, which crosses the placenta. Meta-analysis and observational data show a risk of major malformations about 2 to 3 times the background population risk (2-3%); the risk is dose-dependent and no dose has been found to be without risk. Phenobarbital monotherapy is associated with cleft lip and palate, cardiovascular malformations and other anomalies, and a risk of neurodevelopmental disorders cannot be excluded. Primidone should not be used during pregnancy unless the potential benefit outweighs the risks after considering other suitable options; if used, use the lowest effective dose and ensure the woman fully understands the risks. Third-trimester use may cause neonatal withdrawal symptoms (sedation, hypotonia, sucking disorder). Folic acid supplementation is required before conception and during pregnancy. Do not stop antiepileptic therapy suddenly (section 4.6).

Primidone

Brand names: Mysoline

Primidone is an antiseizure medication used for various seizure types and also for essential tremor; it is largely a prodrug of phenobarbital.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Epilepsy (adults): initially 125 mg as a single intake in the evening; then every 3 days increase the daily dose stepwise by 125 mg until the patient is receiving 500 mg daily; thereafter, every 3 days, increase the daily dose (given in 2 divided doses) by 250 mg until control is obtained or the maximum tolerated dose is reached. Usual maintenance 750 mg to 1500 mg daily

Route: Oral (tablets swallowed whole with a glass of water)

Frequency: Initially a single dose in the evening; maintenance in 2 divided doses

Max: Up to 1.5 g daily in epilepsy; maximum 750 mg daily in essential tremor

Start at the lowest possible dose in the evening and increase stepwise to minimise adverse reactions. If attacks are nocturnal, all or most of the daily dose may be given in the evening; if attacks are linked to a particular event such as menstruation, a slight increase in the appropriate dose is often beneficial. Essential tremor: initially 50 mg daily as a single intake in the late afternoon (using the 50 mg tablet where available), the daily dose (in 2 divided doses) increased gradually over a 2 to 3 week period until remission of symptoms or the highest tolerated dose, up to a maximum of 750 mg daily; patients not previously exposed to anticonvulsants may experience acute intolerance (vertigo, unsteadiness, nausea) so the initial regimen must be respected. Adding to or switching from another anticonvulsant: add primidone with progressive dose increase; when an acceptable therapeutic effect is reached and the primidone dose is at least half the previous dose, attempt withdrawal of the previous treatment progressively over 2 weeks (withdraw phenobarbital and substitute primidone earlier) — withdrawal that is too rapid may precipitate status epilepticus. Children (epilepsy, eMC — age-banded in mg, not per kg): same initial titration (125 mg in the evening, increasing by 125 mg every 3 days to 500 mg daily), then every 3 days increase the daily dose in 2 divided doses by 250 mg in children over 9 years and by 125 mg in children under 9 years; maintenance — over 9 years 750-1500 mg, 6-9 years 750-1000 mg, 2-5 years 500-750 mg, up to 2 years 250-500 mg daily. US labelling additionally quotes a maintenance option of 10 to 25 mg/kg/day in divided doses for children under 8 years (openFDA) — verify all paediatric dosing against a children's formulary before use. Reduced dosage may be required in children, the elderly, debilitated patients and those with impaired renal, hepatic or respiratory function. Primidone is not effective for absence or myoclonic seizures and may aggravate them. Avoid sudden withdrawal — this may induce convulsive fits and status epilepticus.

Dose adjustments

Renal

Renal impairment: renal elimination of primidone is decreased — the dose should be adjusted according to clinical response and biological monitoring. Hepatic impairment: conversion of primidone to its metabolites may be altered and phenobarbital elimination reduced in severe impairment — adjust the dose according to clinical response and monitoring. Elderly patients with reduced renal function receiving primidone should be monitored (section 4.2).

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to primidone, to phenobarbital, or to any of the excipients
Acute intermittent porphyria
Concomitant use with certain classes of medicinal products (SPC section 4.3 refers to section 4.5, which was not captured in the fetched source — verify)

Side effects

Drowsiness, dizziness and ataxia — most common at treatment initiation; may resolve with continued treatment or dose reduction
Visual disturbances, nystagmus, apathy (common); headache and vomiting (uncommon); nausea (common)
Allergic skin reactions including maculopapular, morbilliform or scarlatiniform rashes (uncommon); Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare); DRESS and hypersensitivity syndrome (frequency unknown)
Megaloblastic anaemia, leucopenia, thrombocytopenia, lymphadenopathy (rare)
Osteomalacia, arthralgia, Dupuytren's contracture (rare); decreased bone density, osteopenia, osteoporosis and fractures on long-term therapy (frequency unknown); elevated hepatic enzymes including gamma-GT and alkaline phosphatase (rare)
Suicidal ideation and behaviour have been reported with antiepileptic drugs — monitor patients (section 4.4)

Interactions

Concomitant use with certain classes of medicinal products is contraindicated (section 4.3 cross-refers to section 4.5, which was not included in the fetched source extract — verify against the current SPC)
Primidone is an enzyme (CYP450) inducer and may increase the catabolism of vitamin D; vitamin D supplementation may be needed during long-term therapy, with a dose-dependent increase in the risk of osteomalacia (section 4.4)
Primidone is a potent CNS depressant and is partially metabolised to phenobarbital; after prolonged administration there is potential for tolerance, dependence and a withdrawal reaction on abrupt cessation (section 4.4)
Sudden withdrawal at effective antiepileptic doses may induce convulsive fits and status epilepticus, particularly where alcoholism is also present (section 4.4)

Clinical monograph

How it works

It is metabolised to phenobarbital and phenylethylmalonamide, which enhance GABA-mediated inhibition and reduce neuronal excitability to raise the seizure threshold and dampen tremor.

Prescribing in practice

It is a potent hepatic enzyme inducer that lowers the levels of many co-prescribed drugs, including hormonal contraceptives and anticoagulants, and it must not be stopped abruptly because of the risk of seizures.
Sedation, dizziness and ataxia are common, particularly at the start, so it is introduced at a low dose and titrated slowly.
It carries the teratogenic and dependence risks associated with barbiturates and requires care in older and frail patients.

Monitoring

Monitor for sedation, ataxia and mood change, with full blood count and seizure or tremor control, and be alert to enzyme-induction interactions.

Counselling the patient

Never stop this medicine suddenly, as doing so can trigger seizures.
It often causes drowsiness and unsteadiness when first started, which usually eases; avoid driving until stable.
It can make the contraceptive pill and some other medicines less effective, so seek advice on reliable contraception.

Evidence & guidelines

Primidone is an established treatment for epilepsy and is recognised as a first-line option for essential tremor in clinical guidance, with efficacy supported by long-standing trial evidence.

Reference: NICE NG217; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Pathways